title: Role of metalation in the topoisomerase IIα inhibition and antiproliferation activity of a series of α-heterocyclic-N4-substituted thiosemicarbazones and their Cu(II) complexes.
abstract: The topoisomerase-IIα inhibition and antiproliferative activity of α-heterocyclic thiosemicarbazones and their corresponding copper(II) complexes have been investigated. The Cu(II)(thiosemicarbazonato)Cl complexes were shown to catalytically inhibit topoisomerase-IIα at concentrations (0.3-7.2 μM) over an order of magnitude lower than their corresponding thiosemicarbazone ligands alone. The copper complexes were also shown to inhibit the proliferation of breast cancer cells expressing high levels of topoisomerase-IIα (SK-BR-3) at lower concentrations than cells expressing lower levels of the enzyme (MCF-7).
authors.affiliation: Department of Radiology and the Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, United States.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Zeglis
authors.forename: Vadim
authors.initials: V
authors.lastname: Divilov
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D009584:Nitrogen / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000737:chemistry*; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; D059005:Topoisomerase II Inhibitors; D003300:Copper; D004250:DNA Topoisomerases, Type II; D009584:Nitrogen